There are an estimated 359,000 people living with a diagnosis of a brain tumor in the U.S. Of these tumors, 17,000 are new malignant primary brain tumors and 170,000 are metastatic tumors derived mainly from breast and lung cancer as of 2002. There were an estimated 13,100 deaths per year due to glioma based brain tumors with glioblastoma multiformae being the most aggressive and lethal.
Therapy for treatment of brain cancer is difficult for the following reasons: 1.) Patients are usually diagnosed 6 months to a year before death. Hence, a significant tumor mass is already established by the time treatment is initiated (2) The cancer cells invade normal tissue and do not establish defined barriers, thus surgery yields incomplete removal of residual tumor cells. (3) The brain is protected from the external environment by the blood brain barrier. This barrier is compromised in regions of the brain but there are areas that are still protected and thus accessibility to chemotherapy is restricted. The potency of standard chemotherapy is further reduced by expression of P-glycoprotein encoded by the multidrug resistance-1 (MDR) gene in capillary endothelium of brain capillaries. (4) Many primary tumors metastasize to the brain yielding multiple lesions further complicating therapy. (5) The knowledge base for brain cancer is greatly reduced in comparison to other types of cancer. Making it difficult to define molecular targets and also predicting the course of the disease. Standard therapy is surgical resection and postoperative radiation. Due to the tumor location, complete removal of the tumor may not be possible and some gliomas are completely inoperable.
Gene therapy, the delivery of a therapeutic nucleic acid to a diseased tissue, offers an alternative approach to traditional cancer treatments. In a typical application, genes are targeted to tumor cells to kill the cell or halt the cell's progression through the mitotic cycle. A significant problem in gene therapy-mediated cancer treatment is targeting the gene therapy agent preferentially to cancer cells rather than non-cancerous cells.
Thus there is an urgent need in the art to target therapeutic molecules to cancer cells without affecting the surrounding normal tissue.